Sickle Cell Anemia (SCA) causes different multisystemic manifestations with high morbidity and mortality, mainly characterized by vaso-occlusion, hemolytic anemia and vasculopathy.

We aimed to report a case of two Sickle Cell Anemia Siblings, with different clinical behavior, from the city of Atalaia do Norte, Amazonas, Brazil, assisted and monitored by the HEMOAM Foundation.

ASI*, the oldest brother, currently 19-years old, was diagnosed with Sickle Cell Anemia at the five years old, with few symptoms, no physical abnormalities, stature, and height normal, no hospitalization and without need for blood transfusion. He started using hydroxyurea only at 12-years old and remains stable and with mild comorbidities, needing only sporadic analgesia administration. Her last hemoglobin genotype showed a concentration of 16.7% for Fetal Hemoglobin (HbF). The younger brother, ASI**, aged 17, was diagnosed at the age of 4, with evolution to exuberant symptoms, with an average of eight painful crises/year, mainly in the lower limbs and with several hospitalizations and infectious intercurrences. He had splenomegaly and splenic sequestration, which resulted in splenectomy 1-year after his diagnosis (5-years old). He started using hydroxyurea at the 10-years old, and today he still presents with intense symptoms, cholelithiasis and cholecystectomy at the age of 15 and severe aseptic necrosis of the femoral head, resulting in monthly follow-up with an orthopedist. Her last hemoglobin profile showed a concentration of 7.10% for HbF.

The symptomatological difference between siblings demonstrates that SCA has genetic and non-genetic factors involved in the severity of the disease and its clinical manifestations, which contribute to the clinical heterogeneity of the disease. Currently, at HEMOAM, we are researching candidate genes for sequencing in an attempt to identify possible genetic variants existing in the family and to be able to associate phenotypic complications of the disease with the differences and concomitantly investigate possible hematological, biochemical, immunological and environmental predictors that may influence this clinical diversity.